Thoracic Radiotherapy and Inhibition of PD-1 and LAG-3 for Locally Advanced Non-Small Cell Lung Cancer

Human IgG anti-PD-1 monoclonal antibody approved for treatment of advanced NSCLC with PD-L1 TPS ≥ 50% as monotherapy and in combination with chemotherapy

Human IgG anti-lymphocyte activation gene 3 (LAG-3) monoclonal antibody, which is expressed by various immune cells, and regulates effector T-cell activation and responses. LAG-3 inhibition restores the effector function of exhausted T cells, enhancing their ability to attack tumor cells. Fianlimab is currently under investigation in several clinical studies involving NSCLC (NCT05800015, NCT03916627, NCT05785767).

Thoracic radiotherapy. Conventionally fractionated 1.8-2.0 Gray (Gy) per day. Adaptive radiotherapy will not be performed unless difficulty with patient setup or changes in internal patient anatomy require repeating the CT simulation procedure

Acceptable histology-specific PDC regimens include carboplatin plus paclitaxel or nab-paclitaxel (any histology), carboplatin/cisplatin plus pemetrexed (nonsquamous), carboplatin/cisplatin plus etoposide (any histology), and carboplatin/cisplatin plus docetaxel or gemcitabine (squamous). Carboplatin can be used instead of cisplatin after cycle 1 in cases of cisplatin-induced neuro-/oto-/nephrotoxicity as long as the patient remains eligible for chemoradiotherapy. Weekly radiosensitizing PDC will be recommended for PD-L1 TPS \<50% patients during RT but is not required.